Juberg-Marsidi Syndrome

Synonyms of Juberg-Marsidi Syndrome

General Discussion

Juberg-Marsidi syndrome is an extremely rare X-linked genetic disorder that is fully expressed in males only, and is apparent at birth (congenital) or during the first few weeks of life (neonatal period). Affected children exhibit severe mental retardation; delays in reaching developmental milestones (e.g., crawling, walking, etc.); muscle weakness; diminished muscle tone (hypotonia); and/or delayed bone growth as well as growth retardation, resulting in short stature.

Affected infants also exhibit hearing loss; underdevelopment of the genitals (microgenitalism); and/or abnormalities of the head and facial (craniofacial) area such as an abnormally small head (microcephaly), a flat (depressed) nasal bridge, eye (ocular) abnormalities, and/or, in some cases, additional physical abnormalities. The range and severity of symptoms may vary from case to case. Juberg-Marsidi syndrome is inherited as an X-linked recessive trait.

Signs & Symptoms

Juberg-Marsidi syndrome, an extremely rare inherited disorder, may be apparent at birth (congenital) or during the first few weeks of life (neonatal period). The physical findings and symptoms associated with Juberg-Marsidi syndrome are fully expressed in males only, and the range and severity of such symptoms may vary from case to case. However, some females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder.

In affected males, the primary findings associated with Juberg-Marsidi syndrome are severe mental retardation; hearing loss often resulting in deafness; and/or abnormalities of the genitals such as an abnormally small penis (micropenis) and/or a poorly developed (rudimentary) scrotum into which the testicles may fail to descend (cryptorchidism).

In addition to severe mental retardation, affected males may exhibit delays in reaching developmental milestones (e.g., crawling, sitting, walking, etc.) and/or delayed bone growth as well as growth retardation, resulting in short stature. Affected infants may also exhibit muscle weakness and diminished muscle tone (hypotonia) as well as muscle stiffness and uncontrolled involuntary muscle movements (spasticity). Some affected individuals may be unable to walk.

In addition, affected individuals may have a low birth weight and exhibit malformations of the head and facial (craniofacial) area such as an abnormally small head (microcephaly) with a flat (depressed) nasal bridge and/or abnormalities of the eyes (ocular) such as crossed eyes (strabismus). Due to hearing impairment and developmental delays, some affected individuals may have difficulty talking or be unable to speak.

In some cases, males with Juberg-Marsidi syndrome may also exhibit additional physical abnormalities. For example, in some cases, affected males may have malformed and discolored fingernails and/or toenails (onychodystrophy). In addition, some may also exhibit convulsive seizures.

Females who carry a single copy of the disease gene for Juberg-Marsidi syndrome (heterozygotes) may exhibit some of the symptoms associated with the disorder. Such heterozygous females may exhibit abnormally low intelligence and/or an abnormally small head (microcephaly).

A smaller than normal head (microcephaly) combined usually with underdevelopment of the region about the nose and mouth (midfacial hypoplasia).

Eyes:

Widely spaced eyes (telecanthus), a fold of the eyelid at the inner edge (epicanthic fold).

Nose:

A small triangular nose with prominent upward pointed nostrils and a flat bridge.

Mouth:

A broad mouth with a large tongue that often protrudes; Abnormally located and developed teeth may also be present.

Muscles:

Flaccid, weak muscles from the time of birth (neonatal hypotonia).

Urogenital System:

The scrotum is undeveloped and small associated with undescended or very small testicles and, not infrequently, with a small penis.

Growth and Development:

Short stature is common as is mental retardation.

Other:

Failure to thrive as an infant; Deafness due to nerve damage or underdevelopment of the nerves in the ear.

Causes

Juberg-Marsidi syndrome is inherited as an X-linked recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males can not pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25 percent chance with each pregnancy to have a carrier daughter like themselves, a 25 percent chance to have a non-carrier daughter, a 25 percent to have a son affected with the disease, and a 25 percent chance to have an unaffected son.

In some females who inherit a single copy of the disease gene for Juberg-Marsidi syndrome (heterozygotes), disease traits on the X chromosome may not always be masked by the normal gene on the other X chromosome. As a result, these females may exhibit some of the symptoms associated with the disorder.

The gene that is believed to be involved in Juberg-Marsidi syndrome is located on the long arm (q) of the X chromosome (Xq13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome Xq13″ refers to band 13 on the long arm of the X-chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Juberg-Marsidi syndrome is an extremely rare inherited disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder. Approximately six affected families (kindreds) have been reported in the medical literature. Most symptoms of Juberg-Marsidi syndrome may be apparent at birth or soon thereafter.

Related Disorders

Symptoms of the following disorders can be similar to those of Juberg-Marsidi syndrome. Comparisons may be useful for a differential diagnosis:

Alpha-thalassemia/mental retardation (ATR-X) syndrome, also known as HbH disease, is an extremely rare inherited disorder that is fully expressed in males only. It is characterized by alpha-thalassemia and severe mental retardation. Alpha-Thalassemia is a condition where there is a defect in the production of the oxygen-carrying pigments of red blood cells (hemoglobin). The form of alpha-thalassemia associated with ATR-X syndrome is called Hemoglobulin H (Hb H) disease, which may result in low levels of circulating red blood cells (anemia). Other symptoms include delays in reaching developmental milestones, diminished muscle tone (hypotonia), and/or seizures. Affected infants may also exhibit genital abnormalities including an abnormal fold of skin extending around the base of the penis (shawl scrotum); underdevelopment (hypoplasia) of the scrotum; failure of the testes to descend into the scrotum (cryptorchidism); unusual placement of the urinary opening (meatus) on the underside of the penis (hypospadias); and/or an abnormally small penis (microphallus). In addition, affected infants may also exhibit absence of the kidneys (renal agenesis), and/or abnormal accumulation of urine in the kidney (hydronephrosis). Infants with ATR-X syndrome may also exhibit characteristic facial features including a small, triangular nose; flat bridge of the nose; an extra fold of skin on either side of the nose that may cover the eyes’ inner corners (epicanthal folds); underdevelopment of the middle of the face (midface hypoplasia); and the distance between the upper and lower eyelids may be abnormally large (telecanthus). Alpha-thalassemia/mental retardation (ATR-X) syndrome is inherited as an X-linked trait. ATR-X syndrome and Juberg-Marsidi syndrome are allelic disorders; the mutations that are believed to cause these disorders occur at the same region of the X chromosome. (For more information on this disorder, choose “ATR-X syndrome” as your search term in the Rare Disease Database.)

Borjeson syndrome is an extremely rare inherited disorder characterized by unusual facial features, mental retardation, seizures, short stature, muscle weakness, diminished muscle tone (hypotonia), and/or underdevelopment of the ovaries in females or the testes in males (hypogonadism). Mental retardation may be mild to severe. Characteristic facial features may include an abnormally small head (microcephaly), deep ridges above the eyes (prominent supraorbital ridges), drooping eyelids (ptosis), unusually deep-set eyes, and/or a short neck. Borjeson syndrome, which is thought to be inherited as an X-linked dominant or recessive genetic trait, is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder, and these symptoms are typically less severe than those exhibited by affected males. (For more information on this disorder, choose “Borjeson” as your search term in the Rare Disease Database.)

Gustavson syndrome is an extremely rare inherited disorder that affects both males and females. Symptoms may include mental retardation, an abnormally small head (microcephaly), impaired vision or blindness, hearing abnormalities, muscle stiffness and uncontrolled involuntary muscle movements, epileptic seizures, and limited large joint movement. Gustavson syndrome is thought to be inherited as an X-linked recessive trait.

Diagnosis

Juberg-Marsidi syndrome may be diagnosed at birth or during early infancy, based upon a thorough clinical evaluation and characteristic physical findings. Craniofacial abnormalities, low birth weight, genital malformations, and/or hearing impairment may be apparent at birth. Hearing impairment or deafness may be confirmed through a variety of specialized hearing (auditory) tests. Abnormalities in motor coordination, speech, and intellect may be monitored during infancy and childhood.

Standard Therapies

Treatment

The treatment of this syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, speech pathologists, nutritionists, specialists who assess and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

A variety of methods may be used to treat and correct eye abnormalities. Surgery, corrective glasses, or contact lenses may be used to help improve vision. In some cases, hearing aids may be used for those with hearing impairment.

Early intervention is important in ensuring that affected children with Juberg-Marsidi syndrome reach their potential. Special services that may be beneficial to affected children may include special remedial education and other medical, social, and/or vocational services.

Genetic counseling will be of benefit for affected individuals and their families. Other treatment for Juberg-Marsidi syndrome is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

Resources

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., mental retardation, short stature, hearing impairment, etc.].)

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.

If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

Representatives of patient organizations whose medical advisors are interested in assisting NORD in creating a report on a disease not currently covered in this database may write to orphan@rarediseases.org.